The Neuropathology Core plays a critical role in this Program Project by providing detailed histopathological characterization of a large number of animal and human tissues, utilizing several techniques. In Specific Aim 1, the Core has the task of determining the presence, type, severity and anatomic distribution of the structural lesions, along with the topography and pattern of deposition of the scrapie prion protein (PrPSc) in brains from mice and hamsters. Brains will be sectioned according to precise and fixed coordinates and processed for histological and immunohistochemical examinations. If required, other tissues will be similarly processed. Highly specialized services such as lesion profiling and PET blot and histoblot will also be provided. Altogether, these techniques allow for the establishment of the histopathological phenotype, and are designed to assure that data can be compared. Specific Aim 2 is directed at acquiring and characterizing brain tissues from human prion diseases needed for the coordinated studies of Research Projects 1 and 3. The Core will take advantage of the unique opportunity of acquiring the rare cases needed from the tissue collection of the National Prion Disease Pathology Surveillance Center (NPDPSC), led by the Core Director. The third objective of the Core is to report the results of tissue examinations to the Project Leaders and store processed tissue samples, which will remain available to the members of the Program Project. The qualifications of the Core Director, the variety and consistency of the examinations and access to a unique tissue collection make the Neuropathology Core essential to the success of the entire Program Project. Project